3-132681258-CTTTTTTTTTTTTT-CTTTTTTTTTTTT

Variant names:

• chr3-132681258-CT-C
• rs886058000
• NM_153240.5:c.*651delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_153240.5(NPHP3):​c.*651delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0893 in 105,728 control chromosomes in the GnomAD database, including 318 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.089 (318 hom., cov: 23)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: NPHP3 NM_153240.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

NPHP3 (HGNC:7907): (nephrocystin 3) This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protein interacts with nephrocystin, it is required for normal ciliary development, and it functions in renal tubular development. Mutations in this gene are associated with nephronophthisis type 3, and also with renal-hepatic-pancreatic dysplasia, and Meckel syndrome type 7. Naturally occurring read-through transcripts exist between this gene and the downstream ACAD11 (acyl-CoA dehydrogenase family, member 11) gene. [provided by RefSeq, Feb 2011]

NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-132681258-CT-C is Benign according to our data. Variant chr3-132681258-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1259608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153240.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	NM_153240.5	MANE Select	c.*651delA		3_prime_UTR	Exon 27 of 27	NP_694972.3
	NPHP3-ACAD11	NR_037804.1		n.3995+655delA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHP3	ENST00000337331.10	TSL:1 MANE Select	c.*651delA		3_prime_UTR	Exon 27 of 27	ENSP00000338766.5	Q7Z494-1
	NPHP3-ACAD11	ENST00000632629.1	TSL:2	c.635+655delA		intron	N/A	ENSP00000488520.1	A0A0J9YXS1
	NPHP3	ENST00000971413.1		c.*651delA		splice_region	Exon 25 of 25	ENSP00000641472.1

Frequencies

GnomAD3 genomes AF: 0.0894 AC: 9444 AN: 105646 Hom.: 320 Cov.: 23

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.0952

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.0930

GnomAD4 exome AF: 0.0135 AC: 1 AN: 74 Hom.: 0 Cov.: 0 AF XY: 0.0185 AC XY: 1 AN XY: 54

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0152 AC: 1 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0893 AC: 9436 AN: 105654 Hom.: 318 Cov.: 23 AF XY: 0.0917 AC XY: 4507 AN XY: 49130

African (AFR) AF: 0.116 AC: 3203 AN: 27644

American (AMR) AF: 0.0647 AC: 661 AN: 10212

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 177 AN: 2792

East Asian (EAS) AF: 0.418 AC: 1140 AN: 2728

South Asian (SAS) AF: 0.147 AC: 436 AN: 2976

European-Finnish (FIN) AF: 0.0432 AC: 181 AN: 4194

Middle Eastern (MID) AF: 0.101 AC: 18 AN: 178

European-Non Finnish (NFE) AF: 0.0648 AC: 3425 AN: 52830

Other (OTH) AF: 0.0917 AC: 131 AN: 1428

Alfa AF: 0.0156 Hom.: 8

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886058000; hg19: chr3-132400102;